Parkinson's disease managing reversible neurodegeneration.

Traditionally, the Parkinson's disease (PD) symptom course has been classified as an irreversible progressive neurodegenerative disease. This paper documents 29 PD and treatment-induced systemic depletion etiologies which cause and/or exacerbate the seven novel primary relative nutritional deficiencies associated with PD. These reversible relative nutritional deficiencies (RNDs) may facilitate and accelerate irreversible progressive neurodegeneration, while other reversible RNDs may induce previously undocumented reversible pseudo-neurodegeneration that is hiding in plain sight since the symptoms are identical to the symptoms being experienced by the PD patient. Documented herein is a novel nutritional approach for reversible processes management which may slow or halt irreversible progressive neurodegenerative disease and correct reversible RNDs whose symptoms are identical to the patient's PD symptoms.

Parkinson's disease-associated melanin steal.

Urinary dopamine fluctuations in the competitive inhibition state were first documented in 2009. At that time, it was noted that progressively higher daily dosing values of L-tyrosine decreased the magnitude of these fluctuations. While extensive statistical analysis has been performed by the authors since 2004, it was not until 2012 that a plausible explanation was formulated. In the process, correlations with L-tyrosine administration and the on/off effect of Parkinson's disease were defined. This paper documents the current knowledge with regard to the management of retrograde phase 1 dopamine fluctuations and investigates the hypothesis that they are caused by a melanin steal phenomenon.

Parkinson's disease: carbidopa, nausea, and dyskinesia.

When l-dopa use began in the early 1960s for the treatment of Parkinson's disease, nausea and reversible dyskinesias were experienced as continuing side effects. Carbidopa or benserazide was added to l-dopa in 1975 solely to control nausea. Subsequent to the increasing use of carbidopa has been the recognition of irreversible dyskinesias, which have automatically been attributed to l-dopa. The research into the etiology of these phenomena has identified the causative agent of the irreversible dyskinesias as carbidopa, not l-dopa. The mechanism of action of the carbidopa and benserazide causes irreversible binding and inactivation of vitamin B6 throughout the body. The consequences of this action are enormous, interfering with over 300 enzyme and protein functions. This has the ability to induce previously undocumented profound antihistamine dyskinesias, which have been wrongly attributed to l-dopa and may be perceived as irreversible if proper corrective action is not taken.

The Parkinson's disease death rate: carbidopa and vitamin B6.

The only indication for carbidopa and benserazide is the management of L-3,4-dihydroxyphenylalanine (L-dopa)-induced nausea. Both drugs irreversibly bind to and permanently deactivate pyridoxal 5'-phosphate (PLP), the active form of vitamin B6, and PLP-dependent enzymes. PLP is required for the function of over 300 enzymes and proteins. Virtually every major system in the body is impacted directly or indirectly by PLP. The administration of carbidopa and benserazide potentially induces a nutritional catastrophe. During the first 15 years of prescribing L-dopa, a decreasing Parkinson's disease death rate was observed. Then, in 1976, 1 year after US Food and Drug Administration approved the original L-dopa/carbidopa combination drug, the Parkinson's disease death rate started increasing. This trend has continued to the present, for 38 years and counting. The previous literature documents this increasing death rate, but no hypothesis has been offered concerning this trend. Carbidopa is postulated to contribute to the increasing Parkinson's disease death rate and to the classification of Parkinson's as a progressive neurodegenerative disease. It may contribute to L-dopa tachyphylaxis.

Management of L-dopa overdose in the competitive inhibition state.

The amino acid L-3,4-dihydroxyphenylalanine (L-dopa) is prescribed for conditions where increased central and/or peripheral dopamine synthesis is desired. Its administration can establish dopamine concentrations higher than can be achieved from an optimal diet. Specific indications include Parkinson's disease and restless leg syndrome. The interaction between serotonin and dopamine exists in one of two distinctly different physiologic states: the endogenous state or the competitive inhibition state. Management with L-dopa in the competitive inhibition state is the focus of this paper. In the past, control of the competitive inhibition state was thought to be so difficult and complex that it was described in the literature as functionally "meaningless". When administering L-dopa without simultaneous administration of serotonin precursors, the patient is in the endogenous state. Experience gained with patient outcomes during endogenous L-dopa administration does not allow predictability of L-dopa outcomes in the competitive inhibition state. The endogenous approach typically increases the daily L-dopa dosing value in a linear fashion until symptoms of Parkinson's disease are under control. It is the novel observations made during treatment with the competitive inhibition state approach that L-dopa dosing values above or below the optimal therapeutic range are generally associated with the presence of the exact same Parkinson's disease symptoms with identical intensity. This recognition requires a novel approach to optimization of daily L-dopa dosing values from that used in the endogenous state. This paper outlines that novel approach through utilization of a pill stop. This approach enhances patient safety through its ability to prevent L-dopa overdose, while assisting in the establishment of the optimal therapeutic L-dopa daily dosing value.

Administration of supplemental L-tyrosine with phenelzine: a clinical literature review.

The subject of this literature review is the alleged relationship between L-tyrosine, phenelzine, and hypertensive crisis. Phenelzine (Nardil(®)) prescribing information notes: "The potentiation of sympathomimetic substances and related compounds by MAO inhibitors may result in hypertensive crises (see WARNINGS). Therefore, patients being treated with NARDIL should not take […] L-tyrosine […]". Interest in the scientific foundation of this claim was generated during routine patient care. A comprehensive literature search of Google Scholar and PubMed revealed no reported cases of hypertensive crisis associated with concomitant administration of L-tyrosine and phenelzine. Review of current US Food and Drug Administration nutritional guidelines relating to ongoing phenelzine studies reveals no mention and requires no consideration of L-tyrosine ingestion in combination with phenelzine. This paper is intended to provide an objective review of the science to then allow the reader to formulate the final opinion.

5-HTP efficacy and contraindications.

L-5-hydroxytryptophan (5-HTP) is the immediate precursor of serotonin. It is readily synthesized into serotonin without biochemical feedback. This nutrient has a large and strong following who advocate exaggerated and inaccurate claims relating to its effectiveness in the treatment of depression and a number of other serotonin-related diseases. These assertions are not supported by the science. Under close examination, 5-HTP may be contraindicated for depression in some of the very patients for whom promoters of 5-HTP advocate its use.

Relative nutritional deficiencies associated with centrally acting monoamines.

BACKGROUND: Two primary categories of nutritional deficiency exist. An absolute nutritional deficiency occurs when nutrient intake is not sufficient to meet the normal needs of the system, and a relative nutritional deficiency exists when nutrient intake and systemic levels of nutrients are normal, while a change occurs in the system that induces a nutrient intake requirement that cannot be supplied from diet alone. The purpose of this paper is to demonstrate that the primary component of chronic centrally acting monoamine (serotonin, dopamine, norepinephrine, and epinephrine) disease is a relative nutritional deficiency induced by postsynaptic neuron damage. MATERIALS AND METHODS: Monoamine transporter optimization results were investigated, reevaluated, and correlated with previous publications by the authors under the relative nutritional deficiency hypothesis. Most of those previous publications did not discuss the concept of a relative nutritional deficiency. It is the purpose of this paper to redefine the etiology expressed in these previous writings into the realm of relative nutritional deficiency, as demonstrated by monoamine transporter optimization. The novel and broad range of amino acid precursor dosing values required to address centrally acting monoamine relative nutritional deficiency properly is also discussed. RESULTS: Four primary etiologies are described for postsynaptic neuron damage leading to a centrally acting monoamine relative nutritional deficiency, all of which require monoamine transporter optimization to define the proper amino acid dosing values of serotonin and dopamine precursors. CONCLUSION: Humans suffering from chronic centrally acting monoamine-related disease are not suffering from a drug deficiency; they are suffering from a relative nutritional deficiency involving serotonin and dopamine amino acid precursors. Whenever low or inadequate levels of monoamine neurotransmitters exist, a relative nutritional deficiency is present. These precursors must be administered simultaneously under the guidance of monoamine transporter optimization in order to achieve optimal relative nutritional deficiency management. Improper administration of these precursors can exacerbate and/or facilitate new onset of centrally acting monoamine-related relative nutritional deficiencies.

The discrediting of the monoamine hypothesis.

BACKGROUND: The monoamine hypothesis has been recognized for over half a century as a reference point to understanding electrical dysfunction associated with disease states, and/or regulatory dysfunction related to synaptic, centrally acting monoamine concentrations (serotonin, dopamine, norepinephrine, and epinephrine). METHODS: Organic cation transporters (OCT) are a primary force controlling intracellular and extracellular (including synaptic) concentrations of centrally acting monoamines and their amino acid precursors. A new type of research was analyzed in this paper (previously published by the authors) relating to determining the functional status of the nutritionally driven organic cation transporters. It was correlated with the claims of the monoamine hypothesis. RESULTS: Results of laboratory assays from subjects not suffering from a hyperexcreting tumor show that centrally acting monoamine concentrations are indistinguishable in subjects with and without disease symptoms and/or regulatory dysfunction. Analysis of centrally acting monoamine concentrations in the endogenous state reveals a significant difference in day-to-day assays performed on the same subject with and without monoamine-related disease symptoms and/or regulatory dysfunction. The day-to-day difference renders baseline testing in the endogenous state non-reproducible in the same subject. CONCLUSION: It is asserted that the monoamine hypothesis, which claims that low synaptic levels of monoamines are a primary etiology of disease, is not a valid primary reference point for understanding chronic electrical dysfunction related to the centrally acting monoamines. Furthermore, the "bundle damage theory" is a more accurate primary model for understanding chronic dysfunction. The "bundle damage theory" advocates that synaptic monoamine levels are normal but not adequate in states associated with chronic electrical dysfunction and that levels need to be increased to compensate for the chronic postsynaptic electrical dysfunction due to existing damage. The monoamine hypothesis, in failing to accurately explain the etiology of chronic neuronal electrical flow dysfunction in the endogenous state, is reduced to no more than a historical footnote.

Monoamine depletion by reuptake inhibitors.

BACKGROUND: Disagreement exists regarding the etiology of cessation of the observed clinical results with administration of reuptake inhibitors. Traditionally, when drug effects wane, it is known as tachyphylaxis. With reuptake inhibitors, the placebo effect is significantly greater than the drug effect in the treatment of depression and attention deficit hyperactivity disorder, leading some to assert that waning of drug effects is placebo relapse, not tachyphylaxis. METHODS: Two groups were retrospectively evaluated. Group 1 was composed of subjects with depression and Group 2 was composed of bariatric subjects treated with reuptake inhibitors for appetite suppression. RESULTS: In Group 1, 200 subjects with depression were treated with citalopram 20 mg per day. A total of 46.5% (n = 93) achieved relief of symptoms (Hamilton-D rating score ≤ 7), 37 (39.8%) of whom experienced recurrence of depression symptoms, at which point an amino acid precursor formula was started. Within 1-5 days, 97.3% (n = 36) experienced relief of depression symptoms. In Group 2, 220 subjects were treated with phentermine 30 mg in the morning and citalopram 20 mg at 4 pm. In this group, 90.0% (n = 198) achieved adequate appetite suppression. The appetite suppression ceased in all 198 subjects within 4-48 days. Administration of an amino acid precursor formula restored appetite suppression in 98.5% (n = 195) of subjects within 1-5 days. CONCLUSION: Reuptake inhibitors do not increase the total number of monoamine molecules in the central nervous system. Their mechanism of action facilitates redistribution of monoamines from one place to another. In the process, conditions are induced that facilitate depletion of monoamines. The "reuptake inhibitor monoamine depletion theory" of this paper offers a novel and unified explanation for the waning of response seen after a reuptake inhibitor is started, independent of a drug or placebo etiology.

Validity of urinary monoamine assay sales under the "spot baseline urinary neurotransmitter testing marketing model".

Spot baseline urinary monoamine assays have been used in medicine for over 50 years as a screening test for monoamine-secreting tumors, such as pheochromocytoma and carcinoid syndrome. In these disease states, when the result of a spot baseline monoamine assay is above the specific value set by the laboratory, it is an indication to obtain a 24-hour urine sample to make a definitive diagnosis. There are no defined applications where spot baseline urinary monoamine assays can be used to diagnose disease or other states directly. No peer-reviewed published original research exists which demonstrates that these assays are valid in the treatment of individual patients in the clinical setting. Since 2001, urinary monoamine assay sales have been promoted for numerous applications under the "spot baseline urinary neurotransmitter testing marketing model". There is no published peer-reviewed original research that defines the scientific foundation upon which the claims for these assays are made. On the contrary, several articles have been published that discredit various aspects of the model. To fill the void, this manuscript is a comprehensive review of the scientific foundation and claims put forth by laboratories selling urinary monoamine assays under the spot baseline urinary neurotransmitter testing marketing model.

APRESS: apical regulatory super system, serotonin, and dopamine interaction.

BACKGROUND: THE MONOAMINES SEROTONIN AND DOPAMINE ARE KNOWN TO EXIST IN TWO SEPARATE STATES: the endogenous state and the competitive inhibition state. The presence of the competitive inhibition state has been known to science for many years, but from a functional standpoint it has been noted in the literature as being "meaningless." METHODS: A large database of monoamine transporter response to amino acid precursor administration variations with clinical outcomes was accumulated. In the process, a new organic cation transporter (OCT) model has been published, and OCT functional status determination along with amino acid precursor manipulation methods have been invented and refined. RESULTS: Methodology was developed whereby manipulation of the OCT, in the competitive inhibition state, is carried out in a predictable manner. This, in turn, has disproved the long-held assertion that the monoamine competitive inhibition state is functionally meaningless. CONCLUSION: The most significant aspect of this paper is the documentation of newly recognized relationships between serotonin and dopamine. When transport of serotonin and dopamine are both in the competitive inhibition state, manipulation of the concentrations of one will lead to predictable changes in concentrations of the other. From a functional standpoint, processes regulated and controlled by changes to only serotonin can now be controlled by changes to dopamine, and vice versa, in a predictable manner.

Amino acid management of Parkinson's disease: a case study.

UNLABELLED: An extensive list of side effects and problems are associated with the administration of l-dopa (l-3, 4-dihydroxyphenylalanine) during treatment of Parkinson's disease. These problems can preclude achieving an optimal response with l-dopa treatment. PURPOSE: To present a case study outlining a novel approach for the treatment of Parkinson's disease that allows for management of problems associated with l-dopa administration and discusses the scientific basis for this treatment. PATIENTS AND METHODS: The case study was selected from a database containing 254 Parkinson's patients treated in developing and refining this novel approach to its current state. The spectrum of patients comprising this database range from newly diagnosed, with no previous treatment, to those who were diagnosed more than 20 years before and had virtually exhausted all medical treatment options. Parkinson's disease is associated with depletion of tyrosine hydroxylase, dopamine, serotonin, and norepinephrine. Exacerbating this is the fact that administration of l-dopa may deplete l-tyrosine, l-tryptophan, 5-hydroxytryptophan (5-HTP), serotonin, and sulfur amino acids. The properly balanced administration of l-dopa in conjunction with 5-HTP, l-tyrosine, l-cysteine, and cofactors under the guidance of organic cation transporter functional status determination (herein referred to as "OCT assay interpretation") of urinary serotonin and dopamine, is at the heart of this novel treatment protocol. RESULTS: When 5-HTP and l-dopa are administered in proper balance along with l-tyrosine, l-cysteine, and cofactors under the guidance of OCT assay interpretation, the long list of problems that can interfere with optimum administration of l-dopa becomes controllable and manageable or does not occur at all. Patient treatment then becomes more effective by allowing the implementation of the optimal dosing levels of l-dopa needed for the relief of symptoms without the dosing value barriers imposed by side effects and adverse reactions seen in the past.

Treatment of attention deficit hyperactivity disorder with monoamine amino acid precursors and organic cation transporter assay interpretation.

BACKGROUND: This paper documents a retrospective pilot study of a novel approach for treating attention deficit hyperactivity disorder (ADHD) with amino acid precursors of serotonin and dopamine in conjunction with urinary monoamine assays subjected to organic cation transporter (OCT) functional status determination. The goal of this research was to document the findings and related considerations of a retrospective chart review study designed to identify issues and areas of concern that will define parameters for a prospective controlled study. METHODS: This study included 85 patients, aged 4-18 years, who were treated with a novel amino acid precursor protocol. Their clinical course during the first 8-10 weeks of treatment was analyzed retrospectively. The study team consisted of PhD clinical psychologists, individuals compiling clinical data from records, and a statistician. The patients had been treated with a predefined protocol for administering amino acid precursors of serotonin and dopamine, along with OCT assay interpretation as indicated. RESULTS: In total, 67% of participants achieved significant improvement with only amino acid precursors of serotonin and dopamine. In patients who achieved no significant relief of symptoms with only amino acid precursors, OCT assay interpretation was utilized. In this subgroup, 30.3% achieved significant relief following two or three urine assays and dosage changes as recommended by the assay results. The total percentage of patients showing significant improvement was 77%. CONCLUSION: The efficacy of this novel protocol appears superior to some ADHD prescription drugs, and therefore indicates a need for further studies to verify this observation. The findings of this study justify initiation of further prospective controlled studies in order to evaluate more formally the observed benefits of this novel approach in the treatment of ADHD.

Microperforation prolotherapy: a novel method for successful nonsurgical treatment of atraumatic spontaneous anterior sternoclavicular subluxation, with an illustrative case.

BACKGROUND: Surgical repair of an atraumatic spontaneous anterior subluxation of the sternoclavicular joint (herein referred to as the "SCJ") is often associated with poor outcome expectations. With traditional treatment, successful conservative therapy usually incorporates major lifestyle alterations. This manuscript discusses a novel approach known as "microperforation prolotherapy". To illustrate the technique, the care of a patient who benefitted from this treatment is reviewed. PURPOSE: To present a novel form of treatment with an illustrative case that demonstrates the potential efficacy of microperforation prolotherapy of the SCJ. PATIENT AND METHODS: A novel approach to treatment of bilateral subluxation of the sternoclavicular joint with microperforation prolotherapy is discussed. The clinical course of a 21-year-old male with bilateral subluxation of the SCJ, which seriously hampered the patient's athletic and daily living activities, is used as a backdrop to the discussion. RESULTS: Following microperforation prolotherapy, the instability of the SCJ was replaced by full stability, complete range of motion, and the opportunity to engage in all of the athletic endeavors previously pursued. There is no scar or other cosmetic defect resulting from the treatment received. CONCLUSION: Anterior sternoclavicular joint subluxation has a poor record of complete recovery with surgical procedures or conservative measures with regard to providing restoration of full lifestyle function. This manuscript documents a novel microperforation prolotherapy treatment that induced healing and restored full stability to the ligament structures responsible for the condition in a completely safe and effective fashion, allowing the patient to resume full lifestyle activities without restriction. The exceptional response to treatment noted here is encouragement for further studies.

Urinary neurotransmitter testing: considerations of spot baseline norepinephrine and epinephrine.

BACKGROUND: The purpose of this paper is to present the results of statistical analysis of spot baseline urinary norepinephrine and epinephrine assays in correlation with spot baseline urinary serotonin and dopamine findings previously published by the authors. Our research indicates a need for physicians and decision-makers to understand the lack of validity of this type of spot baseline monoamine testing when using it in the decision-making process for neurotransmitter deficiency disorders. METHODS: Matched-pairs t-tests were performed for a group of subjects for whom spot baseline urinary norepinephrine and epinephrine assays were performed on samples collected on different days then paired by subject. RESULTS: The reported laboratory test results for urinary serotonin, dopamine, norepinephrine, and epinephrine, obtained on different days from the same subjects, differed significantly and were not reproducible. CONCLUSION: Spot baseline monoamine assays, in subjects not suffering from a monoamine-secreting tumor, such as pheochromocytoma or carcinoid syndrome, are of no value in decision-making due to this day-to-day variability and lack of reproducibility. While there have been attempts to integrate spot baseline urinary monoamine assays into treatment of peripheral or central neurotransmitter-associated disease states, diagnosis of neurotransmitter imbalances, and biomarker applications, significant differences in day-to-day reproducibility make this impossible given the known science as it exists today.

A pilot study differentiating recurrent major depression from bipolar disorder cycling on the depressive pole.

PURPOSE: A novel method for differentiating and treating bipolar disorder cycling on the depressive pole from patients who are suffering a major depressive episode is explored in this work. To confirm the diagnosis of type 1 or type 2 bipolar disorder, the Diagnostic and Statistical Manual of Mental Disorders (DSM-IV) criteria require that at least one manic or hypomanic episode be identified. History of one or more manic or hypomanic episodes may be impossible to obtain, representing a potential blind spot in the DSM-IV diagnostic criteria. Many bipolar patients who cycle primarily on the depressive side for many years carry a misdiagnosis of recurrent major depression, leading to treatment with antidepressants that achieve little or no relief of symptoms. This article discusses a novel approach for diagnosing and treating patients with bipolar disorder cycling on the depressive pole versus patients with recurrent major depression. PATIENTS AND METHODS: Patients involved in this study were formally diagnosed with recurrent major depression under DSM-IV criteria and had no medical history of mania or hypomania to support the diagnosis of bipolar disorder. All patients had suffered multiple depression treatment failures in the past, when evaluated under DSM-IV guidelines, secondary to administration of antidepressant drugs and/or serotonin with dopamine amino acid precursors. RESULTS: This study contained 1600 patients who were diagnosed with recurrent major depression under the DSM-IV criteria. All patients had no medical history of mania or hypomania. All patients experienced no relief of depression symptoms on level 3 amino acid dosing values of the amino acid precursor dosing protocol. Of 1600 patients studied, 117 (7.3%) nonresponder patients were identified who experienced no relief of depression symptoms when the serotonin and dopamine amino acid precursor dosing values were adjusted to establish urinary serotonin and urinary dopamine levels in the Phase III therapeutic ranges. All of the 117 nonresponders who achieved no relief of depression symptoms were continued on this amino acid dosing value, and a mood-stabilizing drug was started. At this point, complete relief of depression symptoms, under evaluation with DSM-IV criteria, was noted in 114 patients within 1-5 days. With further dose adjustment of the mood-stabilizing drug, the remaining three nonresponders achieved relief of depression symptoms. CONCLUSION: Resolution of depression symptoms with the addition of a mood-stabilizing drug in combination with proper levels of serotonin and dopamine amino acid precursors was the basis for a clinical diagnosis of bipolar disorder cycling on the depressive pole.

The dual-gate lumen model of renal monoamine transport.

UNLABELLED: The three-phase response of urinary serotonin and dopamine in subjects simultaneously taking amino acid precursors of serotonin and dopamine has been defined.1,2 No model exists regarding the renal etiology of the three-phase response. This writing outlines a model explaining the origin of the three-phase response of urinary serotonin and dopamine. A "dual-gate lumen transporter model" for the basolateral monoamine transporters of the kidneys is proposed as being the etiology of the three-phase urinary serotonin and dopamine responses. PURPOSE: The purpose of this writing is to document the internal renal function model that has evolved in research during large-scale assay with phase interpretation of urinary serotonin and dopamine. PATIENTS AND METHODS: In excess of 75,000 urinary monoamine assays from more than 7,500 patients were analyzed. The serotonin and the dopamine phase were determined for specimens submitted in the competitive inhibition state. The phase determination findings were then correlated with peer-reviewed literature. RESULTS: The correlation between the three-phase response of urinary serotonin and dopamine with internal renal processes of the bilateral monoamine transporter and the apical monoamine transporter of the proximal convoluted renal tubule cells is defined. CONCLUSION: The phase of urinary serotonin and dopamine is dependent on the status of the serotonin gate, dopamine gate, and lumen of the basolateral monoamine transporter while in the competitive inhibition state.

Amino acid-responsive Crohn's disease: a case study.

PURPOSE: This paper reviews the clinical course of a case of severe Crohn's disease and discusses the scientific ramifications of a novel treatment approach. PATIENTS AND METHODS: A case study of a 37-year-old male with a 22-year history of Crohn's disease whose clinical course had experienced no sustained remissions. The patient was treated with a protocol that utilized serotonin and dopamine amino acid precursors administered under the guidance of organic cation transporter assay interpretation. RESULTS: Within 5 days of achieving the necessary balance of serotonin and dopamine, the patient experienced remission of symptoms. This remission has been sustained without the use of any Crohn's disease medications. CONCLUSION: In Crohn's disease, it is known that there is an increase of both synthesis and tissue levels of serotonin in specific locations. It is asserted that this is prima facie evidence of a significant imbalance in the serotonin-dopamine system, leading to serotonin toxicity. The hypothesis formulated is that improperly balanced serotonin and dopamine transport, synthesis, and metabolism is a primary defect contributing to the pathogenesis of Crohn's disease.

Neurotransmitter testing of the urine: a comprehensive analysis.

UNLABELLED: This paper analyzes the statistical correlation of urinary serotonin and dopamine data in subjects not suffering from monoamine-secreting tumors such as pheochromocytoma or carcinoid syndrome. Peer-reviewed literature and statistical analyses were searched and monoamine (serotonin and dopamine) assays defined in order to facilitate their proper interpretation. Many research findings in the literature are novel. Baseline assays completed with no monoamine precursors differ from baseline assays performed on a different day in the same subject. There is currently no scientific basis, value, or predictability in obtaining baseline monoamine assays. Urinary assays performed while taking precursors can demonstrate a lack of correlation or unexpected correlations such as inverse relationships. The only valid model for interpretation of urinary monoamine assays is the "three-phase model" which leads to predictability between monoamine assays and precursor administration in varied amounts. PURPOSE: This paper reviews the basic science of urinary monoamine assays. Results of statistical analysis correlating baseline and nonbaseline assays are reported and provide valid methods for interpretation of urinary serotonin and dopamine results. PATIENTS AND METHODS: Key scientific claims promoting the validity of the urinary neurotransmitter testing (UNT) model applications are discussed. Many of these claims were not supported by the scientific literature. Matched-pairs t-tests were performed on several groupings. Results of all statistical tests were compared with peer-reviewed literature. RESULTS: The statistical analysis failed to support the UNT model. Peer-reviewed literature search failed to verify scientific clams made in support of applications of the UNT model in many cases.